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OBJECTIVE: To evaluate the anti-diabetic efficacy of orally administered bee wax coated water-solu-ble fraction of bee venom(BWCBVA)drug over oral-ly administered bee wax(BW)and intraperitoneally administered whole bee venom(BV)in streptozoto-cin(STZ)-induced diabetic rats.METHODS: Diabetes induced by intraperitoneal ad-ministration of 60 mg/kg STZ was treated with BW-CBVA,BW,and BV for 21 d.The biochemical,pro-tein and histological changes,and physical charac-teristics of BWCBVA were then analyzed.RESULTS: The BWCBVA group shows significantly decreased blood glucose level as compared to the BW and intraperitoneally administered whole BV treated group.Moreover,BWCBVA significantly nor-malizes the serum biochemical parameters and in-creases the body weight.Also,administration of BWCBVA significantly reverses the altered liver ex-pression of phosphatidylinositide 3-kinases-p85 and liver glucokinase.Histological analysis of the pancreas an increase in the islet cell numbers and decrease in β-cell damage.Co-administering BWCB-VA 0.25 mg/kg with nifedipine(6.8 mg/kg)and nicorandil(13.8 mg/kg)to the diabetic rats results in insulin secretion through enhanced calcium ion influx.High performance liquid chromatography and gas chromatography was performed to identi-fy the pharmacologically important compounds present in BWCBVA.CONCLUSION: Our results indicate that BWCBVA,an orally administered colon specific drug deliv-ery system,can be effective in treating diabetes mellitus.